Glycogen synthase kinase 3
Glycogen synthase kinase 3 | ||
---|---|---|
Properties of human protein | ||
Mass / length primary structure | 483 amino acids | |
Secondary to quaternary structure | Monomer | |
Identifier | ||
Gene name | GSK3 | |
External IDs | ||
Enzyme classification | ||
EC, category | 2.7.11.26 , protein kinase | |
Response type | Phosphorylation | |
Substrate | Glycogen synthase, JUN, MYB | |
Occurrence | ||
Homology family | Serine / threonine kinase | |
Parent taxon | Creature |
GSK-3 ( GSK-3 ) is a serine / threonine - protein - kinase , so it is an enzyme which selectively phosphate residues at the serine and threonine residues of other proteins attach (in this case, is it around glycogen synthase ). The phosphorylation of certain target proteins by GSK-3 usually inhibits them.
function
GSK-3 phosphorylates the glycogen synthase , which is thereby inactivated. GSK-3 thus plays a role in the regulation of glycogen synthesis . In the fruit fly Drosophila melanogaster and the clawed frog Xenopus laevis , GSK-3 (here: GSK-3β) is also involved in signal transduction in the Wnt signaling pathway . The kinase works in a protein complex together with adenomatous polyposis coli protein (APC) and the scaffold protein axin and phosphorylates the protein β-catenin . This leads to ubiquitinylation and degradation of β-catenin by proteases, which prevents it from penetrating the cell nucleus and performing its gene regulatory function there. However, when the protein Disheveled is activated via the Wnt signaling pathway, GSK-3 itself is inactivated and β-catenin accumulates in the cytoplasm and in the nucleus, where it performs its regulatory function and activates Wnt target genes.
Research at Stanford University and the University of Karlsruhe showed that the inhibition of GSK-3, for example by LiCl , can serve to treat breast cancer and mixed lineage leukemia (MLL), a form of blood cancer.
GSK-3 deactivation
GSK-3 can be phosphorylated by protein kinase B and thus deactivated. Thus the PKB (protein kinase B) is an activator for the signal transduction pathways which are normally blocked by the GSK-3.
Web links
- Gabriel Marinescu: GSK-3 inhibition triggers apoptosis in tumor cells and inhibits tumor growth in animal models
- Stanford University School of Medicine: New leukemia signal could point way to better treatment, Stanford researchers find